The regulation of gene expression and cellular function is controlled at many different levels in eukaryotic cells. Evidence has been accumulated over the past few years pointing to the importance of mRNA stability, localization, and translation in these processes during development (Berleth, T. et al. (1988) EMBO J. 7:1749-1756; St. Johnston, D. et al. (1991) Cell 92:171-178); Ferrandon, D. et al. (1994) Cell 79:1221-1232) and maintenance of the differentiated phenotype (Wilhelm, J. E. et al. (1993) J. Cell Biol. 123:269-274; Klausner, R. D. et al. (1993) Cell 72:1-28; Hentze, M. W. (1995) Curr. Op. Biol. 7:393-398).
Central to the regulation of these processes are proteins which recognize and bind to specific primary sequences or secondary structures in nucleic acids. Increasing numbers of these proteins are being identified, and a variety of nucleic acid-binding motifs have been recognized (reviewed by Burd, G. C. and G. Dreyfuss (1994) Science 265:615-621). The Y-box family of proteins is perhaps the most evolutionarily conserved group of nucleic acid-binding proteins known. The binding domain of the 70-residue E. coli CS7.4 cold-shock protein is 43% identical to the binding domain of vertebrate Y-box family members. Diverse molecular functions are ascribed to eukaryotic members of the Y-box family including transcription factors and translation control proteins (for reviews, see: Wolffe, A. P. (1994) Bioessays 16:245-251; Burd, C. G. and G. Dreyfuss, supra).
The rat brain RNA-binding protein, PIPPin, has been cloned from an embryonic brain cDNA library. PIPPin is a small hydrophilic protein with a predicted molecular weight of approximately 17 kDa. Amino acid sequence comparisons show that PIPPin has homology to double-stranded RNA-binding proteins from human, mouse, Drosophila, and E. coli, including the E. coli Y-box cold-shock protein (Castiglia, D. et al. (1996) Biochem. Biophys. Res. Comm. 218:390-394).
Northern blot analysis detects only a single PIPPin RNA species in the rat brain at day 18 of embryogenesis. The intensity of this band increases until about day 5 postpartum, and then remains constant into adulthood. The northern blot analysis detects PIPPin RNA only in brain but not in adult liver, kidney, spleen or muscle. These observations indicate that PIPPin is required both during development and maintenance of normal brain functions (Castiglia, D. el al., supra).
The discovery of polynucleotides encoding the novel human RNA-binding protein, and the molecules themselves, provide the means to investigate the regulation of cell growth and maintenance. Discovery of molecules related to rat brain RNA-binding protein, PIPPin, satisfies a need in the art by providing new diagnostic or therapeutic compositions useful for the detection, prevention, and treatment of cancer and inflammatory diseases.